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Introduction: Recently, the use of long-term systemic medications, including biologicals, to manage various chronic systemic diseases has increased. The association between these medications and the pathogenesis or healing of endodontic diseases remains poorly understood. This systematic review aimed to evaluate the relationship between the long-term use of systemic medications and the incidence, prevalence, and/or healing of endodontic diseases and conditions., Methods: A comprehensive literature review was conducted using the electronic MEDLINE Ovid, Scopus, Embase, Cochrane, and PubMed databases followed by manual searching and citation mining for all articles eligible per the inclusion criteria., Results: A total of 2470 citations were screened, and 12 articles met the inclusion criteria and were included in this review. The selected studies included 9 cohort or cross-sectional studies and 3 case-control studies with a low to moderate overall risk of bias mostly. Some medications were associated with either an increased or decreased prevalence of apical periodontitis, whereas other medications were associated with an incidence of pulp calcification or cervical root resorption., Conclusions: Systemic medications may be associated with the incidence, prevalence, or healing of endodontic diseases and conditions, but the level of evidence is low. This warrants more well-designed longitudinal clinical studies on the role of chronic systemic medications as well as controlling for medications when the systemic diseases are studied., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to characterize qualitatively and quantitatively the changes in the endodontic microbiome, in teeth with necrotic pulp, open apexes, and apical periodontitis, with 3 antimicrobial protocols, undertaken in a multicenter clinical trial., Methods: Microbiological samples were collected from 116 regenerative endodontic teeth, and 97 qualified for inclusion. The teeth were randomly divided into 3 treatment groups: apexification (APEX), regeneration (REGEN), and revascularization (REVASC), all in 2 appointments. The group variables in the first appointment irrigants, and second appointment irrigants and medicaments were as follows: APEX: 5.25%-6% NaOCl, 5.25%-6% NaOCl + 17% EDTA and calcium hydroxide; REGEN: 1.25% NaOCl, 17% EDTA, and 0.1 mg/mL triple antibiotic paste (TAP); and REVASC 5.25% NaOCl, saline, and 1 g/mL TAP, respectively. Sampling was done upon access (S0), after irrigation in the first appointment (S1), and after using medication and irrigation in the second appointment (S2)., Results: Quantitative polymerase chain reaction analysis of the 16S ribosomal RNA gene showed significant reduction in bacterial load from S0 to S2 in all groups; however, the APEX and REVASC groups had significantly less residual DNA than the REGEN group (P = .0045). The relative abundance of Bacteroidetes, Fusobacteria, Spirochaetes, and Synergistetes were reduced with the treatment rendered. However, relative abundance of Firmicutes and Actinobacteria was not changed, and that of Proteobacteria increased. LEfSe analysis showed that reduction in bacterial taxa was more in REVASC than APEX, which in turn was more than in REGEN., Conclusion: Enhanced antimicrobial protocols lead to better reduction in quantitative and qualitative parameters of the endodontic microflora., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The first outbreak of coronavirus disease 2019 (COVID-19) in the United States resulted in a nationwide closure of dental offices that created an oral health crisis. The aim of this observational study was to analyze and compare the characteristics of patients who visited 2 private endodontics offices from March 16 to May 31, 2020, compared with the same period in 2019., Methods: Demographic, diagnostic, and procedural data of 1520 (693 in 2020 and 827 in 2019) patient visits were collected. Bivariate and multiple logistic regression analyses were used to assess the impact of the COVID-19 outbreak on patient-related variables., Results: Bivariate analyses showed that the number of patient visits decreased in April and May 2020 (P < .0001). In 2020, patients' self-reported pain level was higher, they were more frequently diagnosed with pulp necrosis and acute apical abscess, and they received more incisions for drainage (P < .05). Multiple logistic regression analyses showed that the COVID-19 outbreak was associated with less visits for older patients (>49.5 years) (odds ratio [OR] = 0.720; 95% confidence interval [CI], 0.573-0.906), more patients with kidney diseases (OR = 2.690; 95% CI, 1.143-6.331), higher levels of pain on percussion (OR = 2.277; 95% CI, 1.718-3.016), less cases with previously initiated treatment (OR = 0.242; 95% CI, 0.080-0.731), less periapical diagnoses of asymptomatic apical periodontitis (OR = 0.510; 95% CI, 0.306-0.849), and a higher number of nonsurgical root canal treatments (OR = 2.073; 95% CI, 1.397-3.074) and apicoectomies (OR = 2.799; 95% CI, 1.367-5.729)., Conclusions: These findings show that the public health burden of endodontic infections was more intense during the initial outbreak of COVID-19., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to investigate microbiota and the histopathology of infected immature teeth microenvironments after disinfection with calcium hydroxide, triple antibiotic paste, and a synthetic antimicrobial peptide (synthetic human beta-defensin-3-C15) for regenerative endodontic procedures (REPs). The null hypothesis was that there is no difference among intracanal medications on disinfection in REPs., Methods: Pulp necrosis and periapical lesions were induced in immature beagle dog premolars. Block randomized teeth were uninfected (negative control, n = 6), left infected (positive control, n = 6), or medicated with a disinfectant (n = 6/group). After disinfection (2 weeks), teeth were reaccessed, irrigated with 17% EDTA, blood clot induced, sealed with ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), and restored with resin-modified glass ionomer. Animals were monitored radiographically and euthanized (12 weeks) for histopathologic and metagenomic analyses., Results: REP-treated roots showed radiographic repair of periapical radiolucency (67.65%, 23/34), continued root development (73.53%, 25/34), and apical closure (70.59%, 24/34) regardless of the disinfectant used (P > .05). Canal microenvironments histologically devoid of bacteria contained new mineralized and pulp-like tissues in characteristic patterns that varied by disinfectant. Next-generation sequencing (16S ribosomal RNA) identified Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes as dominant phyla of microbiota in immature teeth. Infection-induced teeth showed changes in diversity and richness of microbiota from negative controls. Compared with positive controls, all treated teeth exhibited depleted operational taxonomic units, with lower phylogenic diversity from synthetic human beta-defensin-3-C15-treated teeth., Conclusions: There were no differences among the medicaments investigated in radiologic treatment outcomes, but disinfectants in REPs showed altered microbiota from normal and diseased immature teeth with different histologic patterns of regeneration., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: The relationship of apical periodontitis (AP) and type 2 diabetes mellitus (T2DM) is poorly studied in large populations. The aims of this study were to determine if there is an independent association between AP and T2DM in a large hospital network after controlling for confounding variables, as well as to determine if glycated hemoglobin levels were independently associated with AP., Methods: An initial search of the Carolina Data Warehouse for Health yielded 5,995,011 patients, of whom 7,749 were diagnosed with AP in 2015 through 2018. Patients' demographics, T2DM status, HbA 1c , periodontal disease, oral cellulitis, hypertension, atherosclerosis, kidney disease, smoking, body mass index, the use of metformin or statins, and hospital inpatient status were collected from their most recent visit. A control group of 7,749 patients without AP were sampled and matched according to the age, race, and sex of each patient with AP. Multiple logistic regression was used to determine the association between T2DM and AP, as well as between HbA 1c and AP after controlling for the effects of the aforementioned confounding variables, using a matched cohort design., Results: T2DM was independently associated with significantly greater prevalence of AP (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.73 to 2.43). The use of metformin (OR, 0.82; 95% CI, 0.69 to 0.98) or statins (OR, 0.70; 95% CI, 0.62 to 0.78) was independently associated with significantly lower prevalence of AP. HbA 1c greater than 8.0 (OR, 2.46; 95% CI, 1.83 to 3.35) was significantly associated with greater prevalence of AP., Conclusions: T2DM and poorly controlled glycemia were significantly associated with AP. Metformin and statin use were associated with lower prevalence of AP., Practical Implications: This study provides evidence linking T2DM and the level of glycemia to the increased prevalence of AP. Statins and metformin use may be protective in this relationship., (Copyright © 2021 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Patients with pulpal and periapical conditions often seek treatment for pain, intraoral swelling, or both. Even when definitive, conservative dental treatment (DCDT) is an option, antibiotics are often prescribed. The purpose of this review was to summarize available evidence regarding the effect of antibiotics, either alone or as adjuncts to DCDT, to treat immunocompetent adults with pulpal and periapical conditions, as well as additional population-level harms associated with antibiotic use., Type of Studies Reviewed: The authors updated 2 preexisting systematic reviews to identify newly published randomized controlled trials. They also searched for systematic reviews to inform additional harm outcomes. They conducted searches in MEDLINE, Embase, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature. Pairs of reviewers independently conducted study selection, data extraction, and assessment of risk of bias and certainty in the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach., Results: The authors found no new trials via the update of the preexisting reviews. Ultimately, 3 trials and 8 additional reports proved eligible for this review. Trial estimates for all outcomes suggested both a benefit and harm over 7 days (very low to low certainty evidence). The magnitude of additional harms related to antibiotic use for any condition were potentially large (very low to moderate certainty evidence)., Conclusions and Practical Implications: Evidence for antibiotics, either alone or as adjuncts to DCDT, showed both a benefit and a harm for outcomes of pain and intraoral swelling and a large potential magnitude of effect in regard to additional harm outcomes. The impact of dental antibiotic prescribing requires further research., (Copyright © 2019 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Numerous previously undocumented factors may influence the healing of apical periodontitis (AP). The aim of this cohort study was to analyze the association between statin medication intake during the follow-up period and healing of AP., Methods: Patients who self-reported being on statins during nonsurgical root canal treatment or retreatment and patients who reported never taking statins were included. All patients who received treatment on a tooth with periapical radiolucency in the postgraduate endodontics clinic at the University of Maryland School of Dentistry (2011-2014) were invited for follow-up 2 to 5 years after treatment. Healing was determined using the periapical index (PAI). Two calibrated endodontists assessed outcomes blinded to the statin intake. The association of statin intake and healing of endodontic treatment (ie, healed [PAI 1-2]/not healed [PAI 3-5]) was analyzed using the Fisher exact test. Logistic regression analysis was used to explore the association between statin intake and treatment outcome, controlling for the following confounding variables: diabetes mellitus, cardiovascular disease, and smoking, with confidence intervals set at 95%., Results: A total of 60 cases were included in the final analysis, including 30 patients taking statins and 30 patients not taking statins as the control. The Fisher exact test showed significantly higher healing at the 2-year or greater follow-up in patients taking statins compared with controls (93.0% vs 70%; Fisher exact test, P = .02)., Conclusions: The results of this study show a significant association between long-term statin intake and healing of AP after nonsurgical root canal treatment., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: To date, the relationships between systemic diseases and periapical microbial infection remain unknown. Thus the purpose of this systematic review was to evaluate the relationship between host modifying factors and their association with endodontic pathosis., Methods: Two reviewers independently conducted a comprehensive literature search. The MEDLINE, Embase, Cochrane, and PubMed databases were searched. In addition, the bibliographies of all relevant articles and textbooks were manually searched. There was no disagreement between the 2 reviewers., Results: Sixteen articles were identified and included. The overall quality of the studies and the risk of bias were rated to be moderate. Only 3 studies demonstrated a low level of bias., Conclusions: The results of this review suggest that there may be a moderate risk and correlation between some systemic diseases and endodontic pathosis. More prospective and longitudinal research in this area is warranted to determine greater specificity in these possible interactions to potentially decrease or minimize the effects of systemic disease on the formation of apical periodontitis., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This systematic review and meta-analysis investigated evidence to support whether apical periodontitis (AP) can modify the systemic levels of inflammatory markers (IM) in humans., Methods: The MEDLINE, Embase, Cochrane, and PubMed databases were searched between 1948 and 2012, with no language restriction. Additionally, the bibliography of all relevant articles and textbooks were manually searched. Based on inclusion and exclusion criteria, 2 reviewers independently rated the quality of each study based on the Newcastle-Ottawa Scale. The primary outcome variable for meta-analysis was determined by the serum levels of IMs in AP subjects versus healthy controls or in AP subjects before versus after treatment intervention., Results: Among the 531 initially identified articles, 20 comprised the final analysis. Thirty-one different IMs were analyzed, with immunoglobulin (Ig) A, IgM, IgG, and C-reactive protein (CRP) being the most commonly investigated. CRP, interleukin (IL)-1, IL-2, IL-6, asymmetrical dimethylarginine, IgA, IgG, and IgM were shown to be increased in patients with AP compared with controls in most studies. Meta-analyses showed that serum levels of IgA (P = .001), IgG (P = .04), and IgM (P < .00001) were increased in humans with AP compared with healthy controls and serum levels of CRP, IgA, IgE, IgG, and IgM were not significantly different between patients with AP before and after treatment (P > .05)., Conclusions: Available evidence is limited but consistent, suggesting that AP is associated with increased levels of CRP, IL-1, IL-2, IL-6, asymmetrical dimethylarginine, IgA, IgG, and IgM in humans. These findings suggest that AP may contribute to a systemic immune response not confined to the localized lesion, potentially leading to increased systemic inflammation., (Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to investigate the bacterial community profile of intracanal microbiota in primary and persistent endodontic infections associated with asymptomatic chronic apical periodontitis by using GS-FLX Titanium pyrosequencing. The null hypothesis was that there is no difference in diversity of overall bacterial community profiles between primary and persistent infections., Methods: Pyrosequencing analysis from 10 untreated and 8 root-filled samples was conducted., Results: Analysis from 18 samples yielded total of 124,767 16S rRNA gene sequences (with a mean of 6932 reads per sample) that were taxonomically assigned into 803 operational taxonomic units (3% distinction), 148 genera, and 10 phyla including unclassified. Bacteroidetes was the most abundant phylum in both primary and persistent infections. There were no significant differences in bacterial diversity between the 2 infection groups (P > .05). The bacterial community profile that was based on dendrogram showed that bacterial population in both infections was not significantly different in their structure and composition (P > .05)., Conclusions: The present pyrosequencing study demonstrates that persistent infections have as diverse bacterial community as primary infections., (Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The presence of antibiotic resistance genes in endodontic microorganisms might render the infection resistant to common antibiotics. The aims of this project were to identify selected antibiotic resistance genes in primary and persistent endodontic infections and to determine the effectiveness of contemporary endodontic procedures in eliminating bacteria with these genes., Methods: In patients undergoing primary endodontic treatment or retreatment, the root canals were aseptically accessed and sampled before endodontic procedures as well as after contemporary chemomechanical preparation and medication with calcium hydroxide. Identification of the following antibiotic resistance genes was performed by using polymerase chain reaction: bla(TEM-1), cfxA, blaZ, tetM, tetW, tetQ, vanA, vanD, and vanE. Limited phenotypic identification and antibiotic susceptibility verification were also performed., Results: Overall, there were 45 specimens available for analysis, 30 from primary and 15 from persistent endodontic infections. In preoperative specimens, only bla(TEM-1) was significantly more prevalent in primary versus persistent infections (P = .04). After contemporary treatment procedures, there was an overall reduction in prevalence of these genes (P < .001). bla(TEM-1) and tetW were significantly reduced (P < .05), cfxA, blaZ, and tetQ were eliminated, but there was no change in tetM. No specimens contained vanA, vanD, or vanE. Antibiotic susceptibility testing showed significant differences among the antibiotics (P < .001) and general concordance with the gene findings., Conclusions: bla(TEM)(-1) was more prevalent in primary than persistent infections. Vancomycin resistance was not present. The genes identified were reduced with treatment except for tetM. Genetic testing might be useful as a screening tool for antibiotic resistance., (Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: The authors used a custom-built electronic record system to investigate endodontic diagnostic and treatment outcome data in patients with and without diabetes., Methods: The medical histories and endodontic treatment data for nonsurgical endodontic patients treated in predoctoral and postgraduate specialty clinics were entered into an electronic record system. A total of 5,494 cases (including 284 cases in patients with diabetes) were treated, and 540 cases (including 73 cases in patients with diabetes) had follow-up data two years or more postoperatively. The authors performed univariate and multivariate analyses to determine important factors affecting endodontic diagnosis and treatment outcome., Results: Patients with diabetes had increased periodontal disease of teeth with endodontic involvment compared with patients who did not have diabetes. There was a trend toward increased symptomatic periradicular disease in patients with diabetes who received insulin, as well as flareups in all patients with diabetes. Two years or longer postoperatively, 68 percent of cases followed were successful. Older age, the absence of preoperative lesions, the presence of permanent restorations and longer postoperative evaluation periods all were associated with a successful outcome. A multivariate analysis showed that in cases with preoperative periradicular lesions, a history of diabetes was associated with a significantly reduced successful outcome., Conclusions: Patients with diabetes have increased periodontal disease in teeth involved endodontically and have a reduced likelihood of success of endodontic treatment in cases with preoperative periradicular lesions., Clinical Implications: Patients with diabetes who are treated endodontically should be assessed carefully and be treated with effective antimicrobial root canal regimens, particularly in cases with preoperative lesions.

PCR primers that target the bacterial 16S rRNA genes (or the tuf gene for the genus Enterococcus) were used to identify 10 putative bacterial pathogens in root canals with necrotic pulp. In addition, the associations of these microorganisms with symptoms and a history of diabetes mellitus were investigated. Microbial samples from the root canals of 24 teeth with necrotic pulp were included in the study. PCR with universal bacterial primers identified bacterial DNA in 22 specimens; the remaining 2 specimens were from intact teeth that had been traumatized 6 months prior to treatment. PCR with specific primers showed that preoperative symptoms were significantly associated with the presence of Streptococcus spp. (P < 0.001 by chi-square analysis). There was also a nonsignificant trend for symptoms to be associated with Fusobacterium nucleatum and Porphyromonas gingivalis (odds ratio, >2) and for diabetes mellitus to be associated with P. gingivalis and Porphyromonas endodontalis (odds ratio, >2). Cloning and sequencing of the universal PCR product in one specimen revealed the presence of an organism related to the genus Olsenella, which has not previously been described in endodontic infections.

Accurately diagnosing the state of dental pulp is crucial when addressing tooth pain to determine the best treatment approach. This study aimed to investigate the concentration of inflammatory mediators in the dental pulp of mature teeth that have been exposed via caries but show no signs of apical periodontitis. Samples of pulpal blood from adults with mature teeth responsive to pulp testing and have carious pulp exposures were obtained. These samples were analyzed for 12 inflammatory cytokines and other inflammatory proteins using the Luminex assay platform. Clinical factors were correlated with cytokine levels, and statistical analysis was performed to evaluate the impact of these factors on cytokine expression. Of the 36 patients that were included, 44.44% took pain medications, 33.33% had prolonged pulpal bleeding, 41.67% felt spontaneous pain, and 72.22% were diagnosed with symptomatic irreversible pulpitis. Significant correlations existed between presenting pain scores and levels of interleukin (IL)-1α, IL-6, and IL-8 (P <.05). Factors like analgesic medication intake, pain to percussion, pain to thermal testing, spontaneous pain, and nocturnal pain were significantly associated with higher levels of specific inflammatory proteins. No significant associations were observed with pain to palpation, bleeding time, or pulpal diagnosis. Inflammatory proteins, including cytokine levels may play a critical role in characterizing pulpal inflammation. Future studies should investigate the role of these potential biomarkers in determining the diagnosis of pulpitis and the prognosis of vital pulp therapy. [ABSTRACT FROM AUTHOR]